O-15 water, because of its short half-life, is widely used to perform multiple sequential rCBF measurements in one scan session, e.g., in functional mapping studies. Typically, one waits about 12 min to allow for decay of the background before performing the next scan. We have developed a method to perform sequential rCBF measurements more rapidly, by modifying the tracer kinetic equation to account for residual background in blood and brain from a previous scan. Simulation studies demonstrated that there is only a 2-3% increase in the noise in estimates of rCBF due to use of this method. Preliminary data have been obtained in subjects at rest and during visual stimulation, with intervals between 0-15 water injections of 6 min. The % correction in rCBF for residual background ranged from 6% in visual cortex to 17% in white matter. Software has been written to apply this method to PET images on a pixel- by-pixel basis. This will facilitate data analysis comparing the results of activation studies performed with this "fast water" approach to those obtained with the standard method. In addition, we plan to extend this method to semiquantitative 0-15 water studies, when tissue counts are used to map rCBF changes in activation studies. This approach to increase the frequency of rCBF measurements will provide greater flexibility in PET experiments such as brain mapping and studies of acute drug effects on rCBF. Also, it will make such studies easier for patients to tolerate. It will be useful in 3-D imaging studies of single-subjects, in which many more injections of smaller amounts of 0-15 water are used to increase signal-to-noise ratio.